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A Single-Cell Transcriptional Landscape of Emphysema: Heterogeneous Cellular Dynamics in Centrilobular, Panlobular, and Paraseptal Subtypes.

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Τίτλος: A Single-Cell Transcriptional Landscape of Emphysema: Heterogeneous Cellular Dynamics in Centrilobular, Panlobular, and Paraseptal Subtypes.
Συγγραφείς: Hu WP; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China., Zhu JC; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China., Liu L; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China., Wu YX; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China., Wang J; Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China., Zhang J; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Πηγή: International journal of molecular sciences [Int J Mol Sci] 2026 Aug 31; Vol. 27 (17). Date of Electronic Publication: 2026 Aug 31.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, [2000-
Ιατρικοί όροι (MeSH): Pulmonary Emphysema*/classification , Pulmonary Emphysema*/immunology , Pulmonary Emphysema*/metabolism , Transcriptome*, Fibroblasts/metabolism ; Macrophages/metabolism ; Epithelium/metabolism ; Single-Cell Gene Expression Analysis ; Humans ; Male ; Female ; Middle Aged ; Aged ; Immunity, Innate
Περίληψη: Emphysema is a chronic lung disease characterized by irreversible alveolar destruction, with distinct imaging subtypes-centrilobular emphysema (CLE), panlobular emphysema (PLE), and paraseptal emphysema (PSE). The cellular and molecular mechanisms driving subtype-specific pathogenesis remain poorly understood. Here, we performed single-cell RNA sequencing on emphysematous lung tissues from nine patients (three per subtype) to map the transcriptional landscape across CLE, PLE, and PSE. Profiling 84,704 high-quality cells, we identified eight major cell types, and subsequent subclustering uncovered subtype-enriched populations and transcriptional features. CLE was characterized by upregulated inflammatory pathways in ciliated cells and activated macrophage-epithelial/fibroblast crosstalk, suggesting an airway-derived infection and inflammatory phenotype. In PLE, the proportions of Natural Killer T (NKT) cells and Group 1 innate lymphoid cells (ILC1s) with enhanced cytotoxicity were increased, and mesothelial cells showed upregulation of extracellular matrix (ECM)-related genes, indicating dysfunction in innate immune cells and abnormal repair of mesothelial cells. PSE showed pronounced ECM remodeling signatures, with an increased proportion of systemic venous endothelial cells and enhanced fibroblast-epithelial interactions. Collectively, our findings reveal that CLE is predominantly driven by airway-originated inflammation, PSE exhibits a fibrosis-like remodeling phenotype, and PLE represents an intermediate state of innate immune activation and matrix dysregulation, providing a single-cell resolution framework for subtype-specific therapeutic targeting.
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Grant Information: 2023ZD0506205 National Science and Technology Major Project of China; 82203631 National Natural Science Foundation of China; 82270039 National Natural Science Foundation of China; 82300047 National Natural Science Foundation of China; 82570057 National Natural Science Foundation of China
Contributed Indexing: Keywords: centrilobular emphysema; emphysema; panlobular emphysema; paraseptal emphysema; single-cell RNA sequencing
Entry Date(s): Date Created: 20260915 Date Completed: 20260917 Latest Revision: 20260917
Update Code: 20260918
PubMed Central ID: PMC13566781
DOI: 10.3390/ijms27177807
PMID: 42737703
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1422-0067
DOI:10.3390/ijms27177807